title: Genotype-Phenotype Correlation of 2q37 Deletions Including NPPC Gene Associated with Skeletal Malformations.
abstract: Coordinated bone growth is controlled by numerous mechanisms which are only partially understood because of the involvement of many hormones and local regulators. The C-type Natriuretic Peptide (CNP), encoded by NPPC gene located on chromosome 2q37.1, is a molecule that regulates endochondral ossification of the cartilaginous growth plate and influences longitudinal bone growth. Two independent studies have described three patients with a Marfan-like phenotype presenting a de novo balanced translocation involving the same chromosomal region 2q37.1 and overexpression of NPPC. We report on two partially overlapping interstitial 2q37 deletions identified by array CGH. The two patients showed opposite phenotypes characterized by short stature and skeletal overgrowth, respectively. The patient with short stature presented a 2q37 deletion causing the loss of one copy of the NPPC gene and the truncation of the DIS3L2 gene with normal CNP plasma concentration. The deletion identified in the patient with a Marfan-like phenotype interrupted the DIS3L2 gene without involving the NPPC gene. In addition, a strongly elevated CNP plasma concentration was found in this patient. A possible role of NPPC as causative of the two opposite phenotypes is discussed in this study.
authors.affiliation: Laboratorio di Citogenetica, Istituto G. Gaslini, Genova, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tassano
authors.forename: Jens
authors.initials: J
authors.lastname: Buttgereit
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Margherita
authors.initials: M
authors.lastname: Lerone
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Divizia
authors.forename: Renata
authors.initials: R
authors.lastname: Bocciardi
authors.forename: Flavia
authors.initials: F
authors.lastname: Napoli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Pala
authors.forename: Frédérique
authors.initials: F
authors.lastname: Sloan-Béna
authors.forename: Stefania
authors.initials: S
authors.lastname: Gimelli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gimelli
mesh_terms: D001846:Bone Development; D001921:Brain / Q000000981:diagnostic imaging; D002648:Child; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D005095:Exoribonucleases / Q000235:genetics; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008279:Magnetic Resonance Imaging; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D020098:Natriuretic Peptide, C-Type; C571454:DIS3L2 protein, human; D005095:Exoribonucleases